The AAN has published a new guideline on the treatment of spasticity in children and adolescents with cerebral palsy. Lead guideline author Mauricio Delgado, MD, FRCPC, FAAN, spoke with Daniel B. Hoch, MD, PhD, Patient Website Associate Editor, for AAN.com.
AAN.com: Can you briefly summarize your conclusions regarding the efficacy of pharmacologic treatments for childhood spasticity due to cerebral palsy?
Delgado: For localized spasticity botulinum neurotoxin type A (BoNT-A) was found to be an effective treatment to reduce spasticity in the upper and lower extremities. However, there is conflicting evidence regarding functional improvement. BoNT-A was found to be generally safe in children with cerebral palsy (CP). However, the FDA is presently investigating isolated cases of generalized weakness resulting in poor outcomes.
For generalized spasticity, diazepam is probably effective in reducing spasticity, but there is insufficient data on its functional benefits and its side effects. Tizanidine is possibly effective, but there is insufficient data on its effect on function and its side effect profile. There is insufficient evidence to support or refute the use of dantrolene, oral baclofen, and intrathecal baclofen.
AAN.com: How prevalent is spasticity due to cerebral palsy?
Delgado: Cerebral palsy is the most common cause of spasticity in children and the majority of children with CP are affected by it. The prevalence of CP was recently reported to be 3.6 cases per 1,000 in eight-year-old children, with very little variation among Western nations. More than 10,000 babies born in the United States each year will be affected by CP.
AAN.com: What procedures did the group use to review the literature and arrive at its conclusions?
Delgado: Literature searches of MEDLINE and EMBASE were conducted for relevant articles published from 1966 to July 2008 using the following key text and index words: "cerebral palsy," "static encephalopathy," "spasticity," "hypertonia," "children," and "infantile." Key text and index words for the intervention included: "diazepam, " "Valium, " "tizanidine," "Zanaflex," "dantrolene," "Dantrium, "baclofen," "Lioresal," "intrathecal baclofen," "phenol," "alcohol," "botulinum toxin A," "Botox," "Dysport," "BTX-A," "BoNT-A," "botulinum toxin B," "BoNT-B," "BTX-B," "Myobloc," and "Neurobloc."
The inclusion criteria were: all foreign languages with English abstracts, human subjects, peer reviewed, patients 19 years of age or younger with CP, and more than nine patients studied. Citations of review papers from 2000 to 2008 were checked for additional pertinent references.
A total of 978 abstracts were initially found. From these, 528 were identified as potentially pertinent and reviewed in full. Finally, 218 articles were selected that fulfilled the inclusion/exclusion criteria.
Each article was reviewed, abstracted, and classified by at least two authors. Disagreements were resolved by reaching consensus among the reviewers, the first author, and at least two other authors. The AAN's four-tiered classification scheme for therapeutic evidence was used to classify articles, and the strength of the recommendation was linked to the evidence.
AAN.com: How did you define spasticity?
Delgado: We used the definition published by the NIH Task Force on Childhood Motor Disorders in 2003. This definition, which is in agreement with the one by Lance in 1980, was not necessarily stated by the papers reviewed. Most of the papers used the Ashworth or Modified Ashworth Scale to measure "spasticity," which is a scale that is not sensitive for spasticity since it does not take into consideration "velocity" of the muscle stretch. So, the panel accepted the authors' understanding of spasticity at face value. We recognize this is a weakness in most papers published, and that is why we emphasize the need to use more sensitive spasticity scales (i.e., Tardieu). The panel excluded any studies where dystonic or dyskinetic CP patients were included in the analysis.
AAN.com: From a clinical perspective, what does it mean for spasticity to improve, yet absent meaningful functional improvement?
Delgado: Spasticity is only one component of the complex motor disorder that affects patients with cerebral palsy. Weakness and lack of selective motor control may affect function more than spasticity, and they do not necessarily improve by treating the latter. Therefore, function may only improve if spasticity is the predominant symptom affecting the patient. However, we have seen patients improve selective motor control and strength as we reduce spasticity of antagonist muscles.
AAN.com: There were many more Class I and Class II studies of botulinum toxin than of some of the older treatments. To what to do you attribute this disparity?
Delgado: A very good question but I am not totally sure about the answer. I suspect that seeking FDA approval has been a strong motivator for industry to sponsor studies using BoNT-A. Drugs like diazepam, dantrolene and baclofen are generic and have been used for many years. As far as I know, pediatric indication has not been pursued for tizanidine. Intrathecal baclofen obtained FDA approval in 1996 without Class I and II studies, as a device.
AAN.com: Does the paucity of Class I/II evidence for some of the older agents mean that they should not be used?
Delgado: No, the lack of evidence only means that we cannot support or refute their use. In my personal experience, they reduce spasticity, but this has not been scientifically proven.
AAN.com: What further studies are needed?
Delgado: We need to study the older drugs in this population and measure not only their antispasticity effect but also how they can improve the patient's ability to participate in daily activities and how they may impact the quality of life. There is a limited number of drugs available to treat spasticity. In addition, their side effect profile is not very good. Therefore, we need to develop new treatments. We have not had a new antispasticity drug approved for more than 10 years in this country.
Within the past 24 months, Dr. Hoch has received personal compensation for his role as consultant editor for A.D.A.M. Inc. He has also served on the editorial boards of the Journal of Participatory Medicine and AAN.com in the same period. Additionally, his spouse owns greater than $10,000 in stock in Merck, Inc, and Biogen. Dr. Hoch has also served as chart reviewer and expert witness in criminal proceedings at the request of the District Attorney, Essex County, MA.